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MLAB 1415: Hematology Keri Brophy-Martinez Chapter 10: The Hemoglobinopathies Part One Hemoglobinopathies? What are they? ◦ Disorders where the production of normal adult hemoglobin in partly or completely suppressed or replaced by a variant hemoglobin. Hemoglobinopathies Catagories ◦ Inherited abnormality of the structure of one of more of the globin chains ◦ Inherited abnormality related to the rate of synthesis of one or more of the globin chains ◦ Failure of the normal switch from fetal hgb (HbF) to adult hgb (HbA) Broad Classification System for Hemoglobin Disorders Qualitative: ◦ Hemoglobins differ in sequence of amino acids composing globin chain ◦ Disorders called hemoglobinopathies Quantitative: ◦ Characterized by decreased production of hemoglobin resulting from decreased synthesis of one particular globin chain ◦ Called thalassemia Qualitative Disorders Qualitative abnormalities in globin structure, usually involving beta-chain. Heme portion is normal Arise from single amino acid substitution or deletion ◦ Rarely see multiple substitutions. May or may not cause abnormal laboratory test results. Sickle Cell Anemia and Sickle Cell Trait Introduction to Sickle Cell Anemia Most common hemoglobinopathy Autosomal co-dominant Hemoglobin A and Hemoglobin S produced. AS is sickle cell trait. SS is sickle cell disease. Patient is homozygous for HbS (SS). Results in very severe anemia. Frequency African Americans ◦ Sickle cell disease occurs in 0.3-1.35% ◦ Sickle cell trait occurs in 8-10% Is worldwide disorder How and Why Cells Sickle Hb S forms from a point mutation for the sixth amino acid in the Beta chain. Valine substituted for glutamic acid. One benefit for AS persons is increased resistance to malaria Pathophysiology of Sickle Cell Anemia SS cells may look normal when fully oxygenated; Sickling occurs when O2 decreased. Other causes of sickling include decrease in pH and dehydration of patient. Cells become rigid, impeding blood flow to tissues. Tissue death, organ infarction, and pain result. Sickling is reversible up to a point. Have both extravascular hemolysis and intravascular hemolysis. Clinical Findings of Sickle Cell Anemia Clinical signs appear at 6 months of age Have all physical symptoms of anemia Growth and sexual maturation slower Crisis – very painful. Anything that deoxygenates blood acts as trigger (exercise, illness and airplane flights). Sickle cells get stuck in capillaries. Strokes Sickle Cell Anemia: Clinical features Organs Affected: ◦ Liver: Enlarges, malfunctions, jaundice, hyperbilirubinemia ◦ Heart: Cardiomegaly, iron deposits ◦ Spleen: Enlarges leading to infarction and fibrosis Eventually shrivels and becomes nonfunctional ◦ Skin: Develop ulcers, jaundice ◦ Kidney: Hematuria and eventual failure ◦ Lungs: Infarction ◦ Brain: Strokes ◦ Blood: Hemolytic anemia Pathophysiology of Sickle Cell Anemia Have three types of crises: ◦ Aplastic crisis: associated with infections which causes temporary suppression of erythropoiesis. ◦ Hemolytic crisis: Results in exaggerated anemia. ◦ Vaso-occlusive crisis: Associated with severe pain. Hallmark symptom of sickle cell anemia. Peripheral Blood Findings in Sickle Cell Anemia Hb 6-10 g/dL Marked aniso and poik Sickle cells and Target cells Ovalocytes and Schistocytes NRBCs with Polychromasia Increased Retics Basophilic Stippling Howell Jolly Bodies and Pappenheimer Bodies Leukocytosis with left shift Thrombocytosis Special Hematology Tests in Sickle Cell Anemia Electrophoresis on cellulose acetate ◦ Hb S present @ 85-100% Sickling Test – Positive Osmotic Fragility – Decreased Sed Rate – Decreased Chemistry Tests in Sickle Cell Anemia LDH increased Bilirubin – increased Haptoglobin decreased Sickle Cell Anemia: Treatment Prevention of infection Reduce organ damage ◦ Hydroxyurea (it is believed to induce production of Hgb F). Using chemotherapeutic agents ◦ Avoidance of situations that could cause a crisis Minimize pain • Blood transfusion Median age at death ◦ Male: 42 ◦ Female: 48 Sickle Cell Trait Heterozygous AS with more HbA than HbS, so condition is compensated for Patient often has normal life span Usually asymptomatic with occasional episodes of hematuria ◦ Sickling can occur with drastic reduction of oxygen tension such as severe respiratory infection, air travel in unpressurized aircraft, anesthesia or congestive heart failure ◦ Exercise that causes a buildup of lactic acid can cause sickling due to lowered pH Laboratory Features: Sickle Cell Trait Normal CBC – Few target cells or sickle cells may be present. Sickle solubility test – positive. Electrophoresis – Both A and S present. Referenes McKenzie, S. B. (2010). Clinical Laboratory Hematology (2nd ed.). Upper Saddle River, NJ: Pearson Education, Inc. http://learn.genetics.utah.edu/content/disorders/whatare gd/sicklecell/